A nanocapsule shell of poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-b-PLA) mixed with anionic Eudragit S100 (90/10% w/w) was previously used to entrap and define the self-assembly of indigo carmine (IC) within the hydrophilic cavity core. In the present work, binary blends were prepared by solution mixing at different PEG-b-PLA/Eudragit S100 ratios (namely, 100/0, 90/10, 75/25, and 50/50% w/w) to elucidate the role of the capsule shell in tuning the encapsulation of the anionic dye (i.e., IC). The results showed that the higher content of Eudragit S100 in the blend decreases the miscibility of the two polymers due to weak intermolecular interactions between PEG-b-PLA and Eudragit S100. Moreover, with an increase in the amount of Eudragit S100, a higher thermal stability was observed related to the mobility restriction of PEG-b-PLA chains imposed by Eudragit S100. Formulations containing 10 and 25% Eudragit S100 exhibited an optimal interplay of properties between the negative surface charge and the miscibility of the polymer blend. Therefore, the anionic character of the encapsulating agent provides sufficient accumulation of IC molecules in the nanocapsule core, leading to dye aggregates following the self-assembly. At the same time, the blending of the two polymers tunes the IC release properties in the initial stage, achieving slow and controlled release. These findings give important insights into the rational design of polymeric nanosystems containing organic dyes for biomedical applications.

In modern biomedical technology, the fabrication of high-performance sensors for dopamine detection is an important issue because dopamine is a major neurotransmitter and abnormal level of its concentration in the human body is accountable for several neurological diseases. Here, we report a highly sensitive and selective surface plasmon resonance (SPR) sensor modified with small copper oxide nanoparticles (CuO NPs) for experimentally detecting dopamine. Fiber optic sensing probes were fabricated by depositing a 50 nm thick gold film over the unclad portion of a multimode optical fiber using magnetron sputtering, and then further modified with synthesized CuO NPs (~7 nm). Detection of dopamine with the designed SPR sensor was achieved for a wide range of concentrations from very low concentrations with a limit of detection at 1.11 nM and up to 50 nM. The maximum sensitivity was achieved as 0.787 nm/nM and limit of quantification was at 1.43 nM. To evaluate the selectivity of the studied sensor, experiments were also performed with ascorbic acid and uric acid which usually coexist with dopamine in the biological fluids. Moreover, sensing characteristics such as repeatability, linearity, and response time, were studied in detail. Taken together, these findings show that CuO NPs are excellent candidates as SPR sensitizer effectively improving the sensing performance of dopamine.

Composite nanostructures with enhanced photothermal conversion (PTC) play an important role in near infrared (NIR) light-mediated photothermal therapy (PTT) and cancer theranostic applications. However, the diversity and multiplicity of assembled components in a single nanostructured particle produce complexity, so the integrated effects of such a formulation product are difficult to predict and control. In this study, novel composite nanospheres were synthesized by combining only two components with inherent multifunctional properties, i.e., small copper oxide nanoparticles (CuO-NPs) and polydopamine (PDA). The CuO-NPs embedded PDA nanospheres (CuO/PDA-NS) were subjected to material analysis demonstrating strong chelating interactions between the catechol groups of PDA and CuO-NPs surface. This behavior apparently suppresses the release of the embedded CuO-NPs in water, consequently giving the composite nanospheres remarkable stability in aqueous solution (19% copper release in 78 days, pH 7.2). The heating efficiency of CuO/PDA-NS versus water was found to be 66%, which is significantly higher than the heating efficiency of CuO-NPs and PDA-NS (i.e., 50% and 55%, respectively). Additionally, CuO/PDA-NS showed a good thermal stability after consecutive NIR irradiations. Taken together, these results confirm that CuO/PDA-NS exhibit an enhanced thermal effect under NIR laser irradiation, which is expected to lead to great advantages in the treatment of cancer diseases with a minimally invasive approach.

Molecular self-assembly, particularly under 3D spherical confinement, is driven by inherent properties of molecules, as well as the confining system, both play a dominant role in the final self-assembled structure. We recently proposed a novel approach for confinement, in which the core of polymeric nanocapsules was used to entrap organic dye molecules (e.g., indigo carmine), that subsequently organize into rolled up lamellar molecular sheets forming scroll structures. To examine the effect of the confining shell composed by polymeric encapsulating materials, the high molecular weight poly-lactide (PLA) was replaced with low molecular weight poly (lactide-co-glycolide) (PLGA). The PLGA based confining system was prepared by water-in-oil-in-water (W 1 /O/W 2 ) double emulsions. Various techniques were used to analyze the physicochemical properties of the self-assembled dye loaded nanocapsules, in terms of particle morphology, size distribution, surface charge, core content, shell composition, loading capacity, and thermal stability. These techniques also served to evaluate the interactions of the dye and its lamellar nanosheets with the interior wall of the capsule shell. The results show, given the same molecular building unit for self-assembling, that the confining shell charge predominates the spatial growth and the direction of assembled organic dye molecules. This provides a further understanding of the polymeric nanocapsule cavities as an emerging viable platform for practical self-assembling applications.

Molecular self-assembly forms structures of well-defined organization that allow control over material properties, affording many advanced technological applications. Although the self-assembly of molecules is seemingly spontaneous, the structure into which they assemble can be altered by carefully modulating the driving forces. Here we study the self-assembly within the constraints of nanoconfined closed spherical volumes of polymeric nanocapsules, whereby a mixture of polyester-polyether block copolymer and methacrylic acid methyl methacrylate copolymer forms the entrapping capsule shell of nanometric dimensions. We follow the organization of the organic dye indigo carmine that serves as a model building unit due to its tendency to self-assemble into flat lamellar molecular sheets. Analysis of the structures formed inside the nanoconfined space using cryogenic-transmission electron microscopy (cryo-TEM) and cryogenic-electron tomography (cryo-ET) reveal that confinement drives the self-assembly to produce tubular scroll-like structures of the dye. Combined continuum theory and molecular modeling allow us to estimate the material properties of the confined nanosheets, including their elasticity and brittleness. Finally, we comment on the formation mechanism and forces that govern self-assembly under nanoconfinement.

Multifunctional nanocarriers have attracted considerable interest in improving cancer treatment outcomes. Poly(lactide-co-glycolide) (PLGA) nanospheres encapsulating copper oxide nanoparticles (CuO-NPs) are characterized by antitumor activity and exhibit dual-modal contrast-enhancing capabilities. An in vitro evaluation demonstrates that this delivery system allows controlled and sustained release of CuO-NPs. To achieve localized release on demand, an external stimulation by laser irradiation is suggested. Furthermore, to enable simultaneous complementary photothermal therapy, polydopamine (PDA) coating for augmented laser absorption is proposed. To this aim, two formulations of CuO-NPs loaded nanospheres are prepared from PLGA polymers RG-504 H (H-PLGA) and RG-502 H (L-PLGA) as scaffolds for surface modification through in situ polymerization of dopamine and then PEGylation. The obtained CuO-NPs-based multifunctional nanocarriers are characterized, and photothermal effects are examined as a function of wavelength and time. The results show that 808 nm laser irradiation of the coated nanospheres yields maximal temperature elevation (T = 41°C) and stimulates copper release at a much faster rate compared to non-irradiated formulations. Laser-triggered CuO-NP release is mainly depended on the PLGA core, resulting in faster release with L-PLGA, which also yielded potent anti-tumor efficacy in head and neck cancer cell line (Cal-33). In conclusion, the suggested multifunctional nanoplatform offers the integrated benefits of diagnostic imaging and laser-induced drug release combined with thermal therapy.

In this study, we assess the feasibility of highly dense fiber Bragg grating (FBG) arrays for real-time temperature measurement during Nanocomposites (NCs)-enhanced laser ablation (LA) of pancreas tissue. FBG arrays were fabricated with the femtosecond point-by-point writing technology. Each highly dense array contains 25 FBGs with a grating length of 0.9 mm and an edge-to-edge distance of 0.1 mm. As alternative fiber sensors, we used commercially available acrylatecoated FBG arrays containing 5 FBGs. Temperature measurements by the highly dense FBG array were compared to thermal camera readings during laser irradiation of water samples. The augmented thermal effect produced by special NC comprising of a polydopamine matrix embedded with gold and copper was evaluated during the irradiation of an ex vivo phantom. The phantom consisted of a blended porcine pancreas tissue mixed with the NC; tissue mixed with water was used for control. The results clearly demonstrate that the highly dense arrays better detect the peak temperature and temperature distribution. The NC presence increased the maximum temperature reached during LA from 48°C (control) to 90°C (NC) at 2 mm, and from 33 °C to 36°C at 4 mm distance from the laser tip. The low spatial resolution of the commercial arrays produced an underestimation of the peak temperature by 2°C (control), and by 1°C (NC) at 4 mm. These results highlight the importance of the proper selection of the measurement system characteristics, especially when high temperature gradient should be measured in biological tissues undergoing thermal ablation for cancer treatment.

Copper oxide nanoparticles (CuO-NPs) have the potential of serving as an anticancer theranostic agent with photothermal capabilities. In order to control their toxicity and release, the CuO NPs were encapsulated within polymeric nanospheres composed of poly(lactic-co-glycolic acid) (PLGA) core and polydopamine (PDA)/polyethylene glycol (PEG) shell. After the characterization of synthesized nanospheres, their photothermal response to different near-infrared laser sources (808 nm, 940 nm and 1064 nm) was assessed in terms of the measured temperature. Arrays of sub-millimetric fiber Bragg grating sensors were employed to achieve an optimal spatial resolution for resolving the temperature increase in samples embedding the nanospheres. The results have shown that the designed structure of CuO@PLGA/PDA/PEG nanospheres substantially augments the temperature elevation. A maximum of 30 °C temperature increase, in comparison with the control solution, was achieved for the 808 nm laser source. These results indicate that the designed structure of CuO@PLGA/PDA/PEG nanospheres is suitable for further applications towards chemo-photothermal therapy combined with diagnostic imaging for the treatment of cancer.

Copper oxide nanoparticles (CuO NPs) have anticancer and antimicrobial activities. Moreover, they have a contrast enhancing effect in both MRI and ultrasound. Nonetheless, encapsulation is needed to control their toxic side effects and a mechanism for release on demand is required. A methodology is introduced herein for encapsulating and releasing CuO NPs from micelles by ultrasound induced hyperthermia and monitoring the process by MRI. For this aim, CuO NPs loaded poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) micelles were prepared. Then, the profile of copper release with application of ultrasound was examined as a function of time and temperature using a colorimetric method. Finally, T1 weighted MRI images of suspensions and ex vivo poultry liver samples containing the CuO NPs loaded micelles were acquired before and after ultrasound application. The results confirmed that: (i) encapsulated NPs are detectible by MRI T1 mapping, depicting substantial T1 shortening from 1872 ± 62 ms to 683 ± 20 ms. (ii) Ultrasonic hyperthermia stimulated the NPs release with an about threefold increase compared to non-treated samples. (iii) Releasing effect was clearly visible by T1-weighted imaging (mean signal increase ratio of 2.29). These findings can potentially lead to the development of a new noninvasive methodology for CuO NPs based theranostic process.

Copper nanostructures offer remarkable therapeutic potential. In particular, copper oxide nanoparticles (CuO NPs) are increasingly studied for diagnostic and therapeutic purposes. Their anticancer potential, as well as contrast-enhancing capabilities for magnetic resonance imaging (MRI) and ultrasound (US), were previously demonstrated. To further exploit their unique multifunctional capabilities, here CuO NPs were successfully embedded in nanocarriers composed of poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene–glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA) and their release kinetics were studied. The CuO NPs-loaded nanospheres (NS) were obtained with a loading capacity of 3.6% ± 0.6 and 5.6% ± 0.8 respectively, and the copper in vitro release was analyzed over a period of 36 days. Copper release from PLGA-NS was found to follow a zero-order model, while that from PEG-PLGA-NS was best described by the tri-phasic release profile. The Higuchi model showed a higher correlation value (R2) for PLGA-NS and PEG-PLGA-NS (R2 = 0.994 and R2 = 0.959, respectively), suggesting that the release mechanism of CuO NPs is diffusion-controlled. In addition, CuO NPs, encapsulated within these polymeric nanospheres, retained their visibility, as demonstrated by T1-weighted MRI. Our results provide further insights into the benefit of using CuO NPs-loaded PLGA-based nanospheres as multifunctional nanomaterials, which may be considered as a future theranostic agent for multiple applications including drug delivery and imaging.

Bimetallic nanostructures can be attractive contrast-enhancing materials for dual modal imaging, allowing improved diagnosis ability using two different physical phenomena, following administration of a single nanoagent. In this research, the potential of the biocompatible polydopamine (PDA) was explored as a binding matrix to produce CuO NPs embedded in a PDA matrix (CuO@PDA nanocomposite). PDA was then tested as a reducing agent for both CuO NPs and HAuCl4 to yield a PDA composite embedded with gold nanoparticles and copper species, readily available for CT-MRI contrast enhancement. Moreover, in vitro cytotoxicity evaluation implied the low cytotoxicity of Au/Cu@PDA nanocomposite. The procedure, characterization, and imaging experiments focused on a representative Au:Cu atomic ratio of 86:14. The resulting longitudinal magnetic relaxation (T1) and X-ray attenuation properties of the nanocomposite are characterized by using phantom experiments and an ex vivo poultry heart model, demonstrating a consistent contrast improvement with both MRI and CT.

Cancer stem cells, also termed tumor initiating cells (TICs), are a rare population of cells within the tumor mass which initiate tumor growth and metastasis. In pancreatic cancer, TICs significantly contribute to tumor re-growth after therapy, due to their intrinsic resistance. Here we demonstrate that copper oxide nanoparticles (CuO-NPs) are cytotoxic against TIC-enriched PANC1 human pancreatic cancer cell cultures. Specifically, treatment with CuO-NPs decreases cell viability and increases apoptosis in TIC-enriched PANC1 cultures to a greater extent than in standard PANC1 cultures. These effects are associated with increased reactive oxygen species (ROS) levels, and reduced mitochondrial membrane potential. Furthermore, we demonstrate that CuO-NPs inhibit tumor growth in a pancreatic tumor model in mice. Tumors from mice treated with CuO-NPs contain a significantly higher number of apoptotic TICs in comparison to tumors from untreated mice, confirming that CuO-NPs target TICs in vivo. Overall, our findings highlight the potential of using CuO-NPs as a new therapeutic modality for pancreatic cancer.

Copper oxide nanoparticles (CuO-NPs) are increasingly becoming the subject of investigation exploring their potential use for diagnostic and therapeutic purposes. Recent work has demonstrated their anticancer potential, as well as contrast agent capabilities for magnetic resonance imaging (MRI) and through-transmission ultrasound. However, no capability of CuO-NPs has been demonstrated using conventional ultrasound systems, which, unlike the former, are widely deployed in the clinic. Furthermore, in spite of their potential as multifunctional nano-based materials for diagnosis and therapy, CuO-NPs have been delayed from further clinical application due to their inherent toxicity. Herein, we present the synthesis of a novel nanoscale system, composed of CuO-loaded PLGA nanospheres (CuO-PLGA-NS), and demonstrate its imaging detectability and augmented heating effect by therapeutic ultrasound. The CuO-PLGA-NS were prepared by a double emulsion (W/O/W) method with subsequent solvent evaporation. They were characterized as sphere-shaped, with size approximately 200 nm. Preliminary results showed that the viability of PANC-1, human pancreatic adenocarcinoma cells was not affected after 72 h exposure to CuO-PLGA-NS, implying that PLGA masks the toxic effects of CuO-NPs. A systematic ultrasound imaging evaluation of CuO-PLGA-NS, using a conventional system, was performed in vitro and ex vivo using poultry heart and liver, and also in vivo using mice, all yielding a significant contrast enhancement. In contrast to CuO-PLGA-NS, neither bare CuO-NPs nor blank PLGA-NS possess these unique advantageous ultrasonic properties. Furthermore, CuO-PLGA-NS accelerated ultrasound-induced temperature elevation by more than 4 °C within 2 min. The heating efficiency (cumulative equivalent minutes at 43 °C) was increased approximately six-fold, demonstrating the potential for improved ultrasound ablation. In conclusion, CuO-PLGA-NS constitute a versatile platform, potentially useful for combined imaging and therapeutic ultrasound-based procedures.

Abstract Purpose: The aim of this study was to examine the feasibility of using nanoparticle-enhanced transmission ultrasound (NETUS) as an image-based monitoring modality for microwave hyperthermia treatment. Methods: A dedicated transmission ultrasound imaging system was used to obtain acoustic projections and ultrasound computed tomography images. Initially, speed-of-sound based images were used to non-invasively monitor temperature changes in in vitro and ex vivo specimens, induced by a microwave needle-type applicator. Next, the hyperthermia acceleration ability of two ultrasound nanoparticles based contrast agents (iron oxide and copper oxide) was examined and visualised. Finally, a two-step image guided microwave therapeutic procedure using NETUS was investigated in a realistic breast mimicking phantom. First, the pathology simulating region borders were detected. Then, a microwave-induced temperature elevation was non-invasively monitored. Results: The transmission ultrasound scanning system was able to detect temperature changes with a resolution of less than 0.5 °C, both in vitro and ex vivo. In accordance with previous studies, it was visually demonstrated that iron oxide nanoparticles expedite the heating process (p < 0.05). Copper oxide nanoparticles, however, did not alter the hyperthermia profile significantly. In the breast mimicking phantom, NETUS yielded accurate detection of the target region as well as thermal monitoring of the microwave heating procedure. Conclusions: NETUS can combine enhanced target visualisation with non-invasive thermometry and accelerated heating effect. Quantitative feedback, however, requires a tissue-specific calibration-curve. A proof of concept for microwave hyperthermia treatment monitoring using NETUS was established. The suggested methodology may potentially provide a non-invasive cost-effective means for monitoring thermal treatment of the breast.

Combination therapy becomes an important strategy in the management of invasive fungal infections and emergence of resistant fungi mutants. In this work, we examine the combination of copper oxide (CuO) nanoparticles (NPs) with fluconazole as potential treatment against the pathogenic fungi, Candida albicans. CuO NPs (~7 nm in size) were synthesized with acetate ligands assembled on their surface, as shown by both thermal gravimetric analysis and FTIR spectroscopy. Unlike the commercial CuO (both bulk and 50 nm particles), that are poorly dispersed in water, the interaction with water allows the fine dispersion of the coated CuO NPs and their excellent colloidal stability. The addition of fluconazole to the aqueous CuO dispersion induced spontaneous self-assembly of the NPs into linear pearl-like chains network, shown by cryogenic transmission electron microscopy (cryo-TEM). The antifungal activity of the CuO NPs and their combination with fluconazole (fluconazole–CuO NPs) was studied against C. albicans. The best MIC values were obtained at concentrations as low as 0.2 and 0.3 mg/mL, respectively. The results suggest that fluconazole–CuO NPs can provide a potential alternative treatment for C. albicans infections.

The implementation of multimodal imaging in medicine is highly beneficial as different physical properties may provide complementary information, augmented detection ability, and diagnosis verification. Nanoparticles have been recently used as contrast agents for various imaging modalities. Their significant advantage over conventional large-scale contrast agents is the ability of detection at early stages of the disease, being less prone to obstacles on their path to the target region, and possible conjunction to therapeutics. Copper ions play essential role in human health. They are used as a cofactor for multiple key enzymes involved in various fundamental biochemistry processes. Extremely small size copper oxide nanoparticles (CuO-NPs) are readily soluble in water with high colloidal stability yielding high bioavailability. The goal of this study was to examine the magnetic and acoustic characteristics of CuO-NPs in order to evaluate their potential to serve as contrast imaging agent for both MRI and ultrasound. CuO-NPs 7nm in diameter were synthesized by hot solution method. The particles were scanned using a 9.4T MRI and demonstrated a concentration dependent T1 relaxation time shortening phenomenon. In addition, it was revealed that CuO-NPs can be detected using the ultrasonic B-scan imaging. Finally, speed of sound based ultrasonic computed tomography was applied and showed that CuO-NPs can be clearly imaged. In conclusion, the preliminary results obtained, positively indicate that CuO-NPs may be imaged by both MRI and ultrasound. The results motivate additional in-vivo studies, in which the clinical utility of fused images derived from both modalities for diagnosis improvement will be studied.

Multimodal medical imaging is gaining increased popularity in the clinic. This stems from the fact that data acquired from different physical phenomena may provide complementary information resulting in a more comprehensive picture of the pathological state. In this context, nano-sized contrast agents may augment the potential sensitivity of each imaging modality and allow targeted visualization of physiological points of interest (e.g. tumours). In this study, 7 nm copper oxide nanoparticles (CuO NPs) were synthesized and characterized. Then, in vitro and phantom specimens containing CuO NPs ranging from 2.4 to 320 mu g.mL(-1) were scanned, using both 9.4 T MRI and through-transmission ultrasonic imaging. The results show that the CuO NPs induce shortening of the magnetic T1 relaxation time on the one hand, and increase the speed of sound and ultrasonic attenuation coefficient on the other. Moreover, these visible changes are NP concentration-dependent. The change in the physical properties resulted in a substantial increase in the contrast-to-noise ratio (3.4-6.8 in ultrasound and 1.2-19.3 in MRI). In conclusion, CuO NPs are excellent candidates for MRI-ultrasound dual imaging contrast agents. They offer radiation-free high spatial resolution scans by MRI, and cost-effective high temporal resolution scans by ultrasound.

Josephson coupled quantum dot artificial solids were prepared from 20 +/- 4 nm diameter organically functionalized Pb particles. Interparticle separation distances were varied from approximately 26 to 11 Angstrom by varying the passivating organic ligand. Isolated particles were too small to exhibit a Meisner effect by themselves, and so it was possible to employ SQUID magnetometry as a zero-background probe for Cooper pair delocalization in these solids. As the interparticle separation distance was decreased, the quantum dot solids progressed from a Mott insulator to a strongly localized superfluid, and finally to a superfluid.

Films of single-wall carbon nanotubes (SWCNTs) were cast from suspensions in several solvents on the surface of a Pt or Au electrode. Cyclic voltammetry of the films in MeCN did not show well-resolved waves (as distinct from films of C_(60) prepared in a similar manner). However, the increase in the effective capacitance of the electrode with a SWCNT film at 0.5 V vs. an AgQRE was 283 F/g, which is about twice that of carbon electrodes in nonaqueous solvents.